A major goal of neuroscience is to understand the neural processes that link sensory information to the behavior of an organism. The pathways that process visual motion in the fruit fly, Drosophila melanogaster, provide an excellent model system for dissecting the neural circuits that underlie such computations. Despite significant effort and the successful computational modeling of motion vision, the neurological basis for motion detection has yet to be elucidated. The central challenges to understanding neural circuit function are to identify the neurons that participate in each computation, to determine how they are connected to one another, and to assess their functional properties. This proposal develops a novel forward genetic approach based on new transgenic technologies that will achieve these goals. Because forward genetic screens allow the identification of the components of a genetic system in a relatively unbiased manner, they have proven to be extremely powerful tools for understanding many different biological processes, including the mechanisms of development and disease, but have not yet been extensively applied to behavior. Using a sensitive, quantitative behavioral assay, a genetic screen will be carried out to identify neurons that, when disrupted, lead to defects in motion vision. In order to identify the neurons that comprise the motion vision circuitry, it will be necessary to genetically manipulate small, well defined groups of neurons, something that is not possible using current technologies. Because of this, new genetic tools have been developed that allow for systematic dissection of the ensembles of neurons identified in the behavioral screen. Ultimately, studying how these neurons are connected and what their functional properties are should lead to insights into the structure of the neural circuits that process visual information and mediate visual behaviors. These studies will be carried out in the Department of Neurobiology at Stanford University. The applicant will be mentored by two faculty members with expertise spanning the fields of genetics, developmental biology, psychophysical analysis of visual behaviors, and electrophysiology, in insects and primates. The applicant will receive further training by auditing classes, attending seminars, presenting his work in departmental colloquia, and attending a course on quantitative methods in neuroscience at the Woods Hole Marine Biological Lab. PUBLIC HEALTH RELEVANCE: Studies of flies and vertebrates suggest that motion vision represents an evolutionarily ancient computation whose underlying algorithm is conserved across all animals. Therefore, understanding motion vision in flies will be of broad use in understanding the basic neuronal mechanisms of vision and neural computation in both the normal and diseased state.